Despite the fact that most clinical episodes of drug tocicity result from therapy with standard drugs whose use has been approved for many years, financial incentives are apparently lacking to stimulate generation of even the most elementary clincial pharmacological data about many of these agents. The proposed research should provide important data about the metabolism and pharmacokinetics of procainamide, lidocaine and diphenylhydantoin. Gas chromatography-mass spectrometry will be relied on heavily for these investigations, and the availabiltiy of stable isotope labelled compounds will be exploited for both the metabolism and pharmacokinetic studies. The later investigations will entail development of new uses for stable isotope labelled compounds in pharmacokinetic research. An attempt will be made not only to identify metabolites of these drugs, but to establish their clinical relevance by studying the pharmacological activity of these compounds. In some cases this may lead to the development of an improved new drug. Another investigation is planned to explore the mechanism by which nitrofuran analogs inhibit ADP-induced platelet aggregation. Quantum mechanical calculations will be used to help correlate the structure of these compounds with their activity, and, once such correlations are establised, to design new compounds of possible therapeutic value as anticoagulants.